Publications

TitleAbstractYear(sorted ascending)
Filter
PMID
Filter
characterization of in vitro chlamydia muridarum persistence and utilization in an in vivo mouse model of chlamydia vaccine.chlamydia trachomatis genital tract infections are easily treated with antibiotics; however, the majority of infections are asymptomatic and therefore untreated, highlighting the need for a vaccine. because most infections are asymptomatic, vaccination could potentially be administered to individuals who may have an acute infection at that time. in such individuals, the effect of vaccination on the existing infection is unknown; however, one potential outcome could be the development of a persis ...201323414449
usefulness of 11c-choline positron emission tomography for genital chlamydial infection assessment in a balb/c murine model.the aim of this study is to explore the feasibility of 11c-choline pet in the assessment of the degree of inflammation in the chlamydia muridarum genital infection model.201323362001
chlamydial infection in vitamin d receptor knockout mice is more intense and prolonged than in wild-type mice.vitamin d hormone (1,25-dihydroxyvitamin d) is involved in innate immunity and induces host defense peptides in epithelial cells, suggesting its involvement in mucosal defense against infections. chlamydia trachomatis is a major cause of bacterial sexually transmitted disease worldwide. we tested the hypothesis that the vitamin d endocrine system would attenuate chlamydial infection. vitamin d receptor knock-out mice (vdr(-/-)) and wild-type mice (vdr(+/+)) were infected with 10(3) inclusion for ...201323201171
enhanced inducible costimulator ligand (icos-l) expression on dendritic cells in interleukin-10 deficiency and its impact on t-cell subsets in respiratory tract infection.an association between inducible costimulator ligand (icos-l) expression and interleukin (il)-10 production by dendritic cells (dcs) has been commonly found in infectious disease. dcs with higher icos-l expression and il-10 production are reportedly more efficient in inducing regulatory t cells (tregs). here we use the chlamydia muridarum (cm) lung infection model in il-10 knockout (ko) mice to test the relationship between il-10 production and icos-l expression by dcs. we examined icos-l expres ...201324100657
the duration of chlamydia muridarum genital tract infection and associated chronic pathological changes are reduced in il-17 knockout mice but protection is not increased further by immunization.il-17 is believed to be important for protection against extracellular pathogens, where clearance is dependent on neutrophil recruitment and local activation of epithelial cell defences. however, the role of il-17 in protection against intracellular pathogens such as chlamydia is less clear. we have compared (i) the course of natural genital tract c. muridarum infection, (ii) the development of oviduct pathology and (iii) the development of vaccine-induced immunity against infection in wild type ...201324073293
cd4+ t cell expression of myd88 is essential for normal resolution of chlamydia muridarum genital tract infection.resolution of chlamydia genital tract infection is delayed in the absence of myd88. in these studies, we first used bone marrow chimeras to demonstrate a requirement for myd88 expression by hematopoietic cells in the presence of a wild-type epithelium. using mixed bone marrow chimeras we then determined that myd88 expression was specifically required in the adaptive immune compartment. furthermore, adoptive transfer experiments revealed that cd4(+) t cell expression of myd88 was necessary for no ...201324038087
cd1d-restricted nkt cells modulate placental and uterine leukocyte populations during chlamydial infection in mice.invariant cd1d-restricted natural killer t cells play an important immunoregulatory role and can influence a broad spectrum of immunological responses including against bacterial infections. they are present at the fetal-maternal interface and although it has been reported that experimental systemic inkt cell activation can induce mouse abortion, their role during pregnancy remain poorly understood. in the present work, using a physiological chlamydia muridarum infection model, we have shown tha ...201323999314
intracellular survival and persistence of chlamydia muridarum is determined by macrophage polarization.macrophages can display a number of distinct phenotypes, known collectively as polarized macrophages. the best defined of these phenotypes are the classically-activated, interferon gamma (ifnγ)/lps induced (m1) and alternatively-activated, il-4 induced (m2) macrophages. the goal of this study is to characterize macrophage-chlamydia interactions in the context of macrophage polarization. here we use chlamydia muridarum and murine bone-marrow derived macrophages to show chlamydia does not induce m ...201323967058
cd4⁺cd25⁺foxp3⁺ regulatory t cells promote th17 responses and genital tract inflammation upon intracellular chlamydia muridarum infection.the functional role of cd4⁺cd25⁺foxp3⁺ regulatory t cells (tregs) in host responses to intracellular bacterial infection was investigated in an in vitro coculturing system and a murine model of chlamydia muridarum genital tract infection. remarkably, c. muridarum infection subverted the immune suppressive role of cd4⁺cd25⁺foxp3⁺ tregs; instead of hampering immune responses, tregs not only promoted th17 differentiation from conventional cd4⁺ t cells but also themselves converted into proinflammat ...201323956419
ifn-ε is constitutively expressed by cells of the reproductive tract and is inefficiently secreted by fibroblasts and cell lines.type-i interferons (ifns) form a large family of cytokines that primarily act to control the early development of viral infections. typical type-i ifn genes, such as those encoding ifn-α or ifn-β are upregulated by viral infection in many cell types. in contrast, the gene encoding ifn-ε was reported to be constitutively expressed by cells of the female reproductive tract and to contribute to the protection against vaginal infections with herpes simplex virus 2 and chlamydia muridarum. our data c ...201323951133
oviduct infection and hydrosalpinx in dba1/j mice is induced by intracervical but not intravaginal inoculation with chlamydia muridarum.intravaginal infection with c. muridarum in mice often results in hydrosalpinx similar to that found in women urogenitally infected with c. trachomatis, making the c. muridarum lower genital tract infection murine model suitable for studying c. trachomatis pathogenesis. to our surprise, dba1/j mice were highly resistant to hydrosalpinx following an intravaginal infection with c. muridarum although these mice were as susceptible to lower genital tract infection as other mouse strains. a significa ...201323940777
chlamydia trachomatis infection of the male genital tract: an update.chlamydia trachomatis (ct) is the most prevalent cause of sexually transmitted diseases. although the prevalence of chlamydial infection is similar in men and women, current research and screening are still focused on women, who develop the most severe complications, leaving the study of male genital tract (mgt) infection underrated. herein, we reviewed the literature on genital ct infection with special focus on the mgt. data indicate that ct certainly infects different parts of the mgt such as ...201323870458
chlamydial infection of the gastrointestinal tract: a reservoir for persistent infection.the mechanism by which chlamydiae persist in vivo remains undefined; however, chlamydiae in most animals persist in the gastrointestinal tract (gi) and are transmitted via the fecal-oral route. oral infection of mice with chlamydia muridarum was previously shown to establish a long-term persistent infection in the gi tract. in this study, balb/c, dba/2, and c57bl/6 mice, infected orally with c. muridarum, were infected in the cecum for as long as 100 days in the absence of pathology. the primary ...201323843274
identification of a serine protease inhibitor which causes inclusion vacuole reduction and is lethal to chlamydia trachomatis.the mechanistic details of the pathogenesis of chlamydia, an obligate intracellular pathogen of global importance, have eluded scientists due to the scarcity of traditional molecular genetic tools to investigate this organism. here we report a chemical biology strategy that has uncovered the first essential protease for this organism. identification and application of a unique cthtra inhibitor (jo146) to cultures of chlamydia resulted in a complete loss of viable elementary body formation. jo146 ...201323796320
contribution of interleukin-12 p35 (il-12p35) and il-12p40 to protective immunity and pathology in mice infected with chlamydia muridarum.the p35 molecule is unique to interleukin-12 (il-12), while p40 is shared by both il-12 and il-23. il-12 promotes th1 t cell responses, while il-23 promotes th17 t cell responses. the roles of il-12p35- and il-12p40-mediated responses in chlamydial infection were compared in mice following an intravaginal infection with chlamydia muridarum. mice deficient in either il-12p35 or p40 both developed similar but prolonged infection time courses, confirming the roles of il-12-mediated immune responses ...201323753624
intranasal vaccination with chlamydia pneumoniae induces cross-species immunity against genital chlamydia muridarum challenge in mice.chlamydia trachomatis is the most common bacterial sexually transmitted disease in the world and specifically in the united states, with the highest incidence in age-groups 14-19 years. in a subset of females, the c. trachomatis genital infection leads to serious pathological sequelae including pelvic inflammatory disease, ectopic pregnancy, and infertility. chlamydia pneumoniae, another member of the same genus, is a common cause of community acquired respiratory infection with significant numb ...201323741420
perforin is detrimental to controlling [corrected] c. muridarum replication in vitro, but not in vivo.cd4 t cells are critical for clearing experimental chlamydia muridarum genital tract infections. two independent in vitro cd4 t cell mechanisms have been identified for terminating chlamydia replication in epithelial cells. one mechanism, requiring ifn-γ and t cell-epithelial cell contact, terminates infection by triggering epithelial production of nitric oxide to chlamydiacidal levels; the second is dependent on t cell degranulation. we recently demonstrated that there are two independent in vi ...201323691028
a t cell epitope-based vaccine protects against chlamydial infection in hla-dr4 transgenic mice.vaccination with recombinant chlamydial protease-like activity factor (rcpaf) has been shown to provide robust protection against genital chlamydia infection. adoptive transfer of ifn-γ competent cpaf-specific cd4⁺ t cells was sufficient to induce early resolution of chlamydial infection and reduction of subsequent pathology in recipient ifn-γ-deficient mice indicating the importance of ifn-γ secreting cd4⁺ t cells in host defense against chlamydia. in this study, we identify cd4⁺ t cell reactiv ...201324096029
b cells enhance antigen-specific cd4 t cell priming and prevent bacteria dissemination following chlamydia muridarum genital tract infection.b cells can contribute to acquired immunity against intracellular bacteria, but do not usually participate in primary clearance. here, we examined the endogenous cd4 t cell response to genital infection with chlamydia muridarum using mhc class-ii tetramers. chlamydia-specific cd4 t cells expanded rapidly and persisted as a stable memory pool for several months after infection. while most lymph node chlamydia-specific cd4 t cells expressed t-bet, a small percentage co-expressed foxp3, and rorγt-e ...201324204262
a vaccine formulated with a combination of tlr-2 and tlr-9 adjuvants and the recombinant major outer membrane protein elicits a robust immune response and significant protection against a chlamydia muridarum challenge.chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in the world and there is a need for a vaccine. to enhance the immunogenicity of a vaccine formulated with the chlamydia muridarum (cm) mouse pneumonitis recombinant major outer membrane protein (momp), we used combinations of pam2csk4 + cpg-1826 and montanide isa 720 vg + cpg-1826 as adjuvants. neisseria gonorrhoeae recombinant porin b (ng-porb) was used as the antigen control with the same adjuvants. female balb/c ...201324291713
assessment of the role in protection and pathogenesis of the chlamydia muridarum v-type atp synthase subunit a (atpa) (tc0582).a novel chlamydia muridarum antigen (tc0582) was used to vaccinate balb/c mice. mice were also immunized with other components of the atp synthase complex (tc0580, tc0581, and tc0584), or with the major outer membrane protein (momp). tc0582 was also formulated in combination with tc0580, tc0581 or momp. tc0582 alone, or in combination with the other antigens, elicited strong chlamydia-specific humoral and cellular immune responses. vaccinated animals were challenged intranasally and the course o ...201324161793
vaccination with major outer membrane protein proteosomes elicits protection in mice against a chlamydia respiratory challenge.vaccines formulated with the chlamydia muridarum native major outer membrane protein (nmomp) have so far been shown to elicit the most robust protection against this pathogen. nmomp is a membrane protein and therefore, detergents are used to keep it in solution. detergents however, have toxic effects. to address this limitation, we tested a nmomp proteosome vaccine and compared its ability to elicit protection against nmomp solubilized in the detergent z3-14. the two preparations were formulated ...201323999313
vaccination with the recombinant major outer membrane protein elicits antibodies to the constant domains and induces cross-serovar protection against intranasal challenge with chlamydia trachomatis.to determine the ability of the major outer membrane protein (momp) to elicit cross-serovar protection, groups of mice were immunized by the intramuscular (i.m.) and subcutaneous (s.c.) routes with recombinant momp (rmomp) from chlamydia trachomatis serovars d (uw-3/cx), e (bour), or f (ic-cal-3) or chlamydia muridarum strain nigg ii using cpg-1826 and montanide isa 720 vg as adjuvants. negative-control groups were immunized i.m. and s.c. with neisseria gonorrhoeae recombinant porin b (ng-rporb) ...201323478318
recombinant outer membrane vesicles carrying chlamydia muridarum htra induce antibodies that neutralize chlamydial infection in vitro.outer membrane vesicles (omvs) are spheroid particles released by all gram-negative bacteria as a result of the budding out of the outer membrane. since they carry many of the bacterial surface-associated proteins and feature a potent built-in adjuvanticity, omvs are being utilized as vaccines, some of which commercially available. recently, methods for manipulating the protein content of omvs have been proposed, thus making omvs a promising platform for recombinant, multivalent vaccines develop ...201324009891
plasmid cds5 influences infectivity and virulence in a mouse model of chlamydia trachomatis urogenital infection.the native plasmid of both chlamydia muridarum and chlamydia trachomatis has been shown to control virulence and infectivity in mice and in lower primates. we recently described the development of a plasmid-based genetic transformation protocol for chlamydia trachomatis that for the first time provides a platform for the molecular dissection of the function of the chlamydial plasmid and its individual genes or coding sequences (cds). in the present study, we transformed a plasmid-free lymphogran ...201424866804
interleukin-22 promotes t helper 1 (th1)/th17 immunity in chlamydial lung infection.the role of interleukin-22 (il-22) in intracellular bacterial infections is a controversial issue, although the contribution of this cytokine to host defense against extracellular bacterial pathogens has been well established. in this study, we focused on an intra-cellular bacterium, chlamydia, and evaluated the production and function of il-22 in host defense against chlamydial lung infection using a mouse model. we found that chlamydia muridarum infection elicited quick il-22 responses in the ...201424531835
plasmid-encoded pgp3 is a major virulence factor for chlamydia muridarum to induce hydrosalpinx in mice.hydrosalpinx induction in mice by chlamydia muridarum infection, a model that has been used to study c. trachomatis pathogenesis in women, is known to depend on the cryptic plasmid that encodes eight genes designated pgp1 to pgp8. to identify the plasmid-encoded pathogenic determinants, we evaluated c. muridarum transformants deficient in the plasmid-borne gene pgp3, -4, or -7 for induction of hydrosalpinx. c. muridarum transformants with an in-frame deletion of either pgp3 or -4 but not -7 fail ...201425287930
the mucosal expression pattern of interferon-ε in rhesus macaques.type i ifns play an important role in innate and adaptive immunity against viral infections. a novel type i ifn, namely ifn-ε, which can protect against vaginal transmission of hsv2 and chlamydia muridarum bacterial infection, has been described in mice and humans. nevertheless, the principle cell type and the expression pattern of ifn-ε in tissues remain uncertain. in addition, the expression of ifn-ε in indian rhesus macaques (macaca mulatta) has not been reported. here, we analyzed ifn-ε expr ...201425139290
reply to letter to the editor re: "in vivo whole animal body imaging reveals colonization of chlamydia muridarum to the lower genital tract at early stages of infection". 201425082537
letter to the editor re: in vivo whole animal body imaging reveals colonization of chlamydia muridarum to the lower genital tract at early stages of infection. 201425080324
protection promoted by pgp3 or pgp4 against chlamydia muridarum is mediated by cd4(+) cells in c57bl/6n mice.urogenital tract infection with chlamydia trachomatis is a leading cause of sexually transmitted infections. there is currently no commercially available vaccine against c. trachomatis. the highly conserved plasmid of chlamydiae has been considered to be a virulence factor and the plasmid proteins have important roles in the chlamydia-specific immune response. this study was designed to evaluate the efficacy of vaccination with plasmid proteins in the prevention of c. muridarum lung infection in ...201425077421
benzylidene acylhydrazides inhibit chlamydial growth in a type iii secretion- and iron chelation-independent manner.chlamydiae are widespread gram-negative pathogens of humans and animals. salicylidene acylhydrazides, developed as inhibitors of type iii secretion system (t3ss) in yersinia spp., have an inhibitory effect on chlamydial infection. however, these inhibitors also have the capacity to chelate iron, and it is possible that their antichlamydial effects are caused by iron starvation. therefore, we have explored the modification of salicylidene acylhydrazides with the goal to uncouple the antichlamydia ...201424914180
complement factor c5 but not c3 contributes significantly to hydrosalpinx development in mice infected with chlamydia muridarum.hydrosalpinx is a pathological hallmark of tubal infertility associated with chlamydial infection. however, the mechanisms of hydrosalpinx remain unknown. here, we report that complement factor 5 (c5) contributes significantly to chlamydial induction of hydrosalpinx. mice lacking c5 (c5(-/-)) failed to develop any hydrosalpinx, while ∼42% of the corresponding wild-type mice (c5(+/+)) did so following intravaginal infection with chlamydia muridarum. surprisingly, deficiency in c3 (c3(-/-)), an up ...201424842924
increased immunoaccessibility of momp epitopes in a vaccine formulated with amphipols may account for the very robust protection elicited against a vaginal challenge with chlamydia muridarum.there is a need to implement a vaccine to protect against chlamydia trachomatis infections. to test a new vaccine, mice were immunized with the chlamydia muridarum native major outer membrane protein (nmomp) solubilized with either amphipol a8-35 or the detergent z3-14. ova was used as a negative control, and mice were inoculated intranasally with c. muridarum as positive controls. animals vaccinated with nmomp mounted strong chlamydia-specific humoral and cell-mediated immune responses. mice va ...201424778450
in vivo whole animal body imaging reveals colonization of chlamydia muridarum to the lower genital tract at early stages of infection.the leading cause of sexually transmitted bacterial infection is chlamydia trachomatis. the aim of this study is to investigate the early events in colonization of this bacterium within the murine genital tract.201424723309
lack of long-lasting hydrosalpinx in a/j mice correlates with rapid but transient chlamydial ascension and neutrophil recruitment in the oviduct following intravaginal inoculation with chlamydia muridarum.lower genital tract infection with chlamydia trachomatis and c. muridarum can induce long-lasting hydrosalpinx in the upper genital tract of women and female mice, respectively. however, a/j mice were highly resistant to induction of long-lasting hydrosalpinx by c. muridarum. we further compared host inflammatory responses and chlamydial infection courses between the hydrosalpinx-resistant a/j mice and cba/j mice known to be susceptible to hydrosalpinx induction. both mouse strains developed rob ...201424711570
the genetic basis of plasmid tropism between chlamydia trachomatis and chlamydia muridarum.the development of genetic transformation technology for chlamydia trachomatis using its endogenous plasmid has recently been described. chlamydia muridarum cannot be transformed by the c. trachomatis plasmid, indicating a barrier between chlamydial species. to determine which regions of the plasmid conferred the species specificity, we used the novel approach of transforming wild-type c. muridarum carrying the endogenous plasmid pnigg and forced recombination with the c. trachomatis vector pgfp ...201424700815
steroids alone or as adjunctive therapy with doxycycline fail to improve oviduct damage in mice infected with chlamydia muridarum.in women, chlamydia trachomatis can ascend from the cervix to the fallopian tubes, where an overly aggressive host inflammatory response can cause scarring that leads to chronic pelvic pain, infertility, or ectopic pregnancy. although screening and treatment programs for women have resulted in decreased rates of sequelae, morbidities associated with oviduct scarring continue to occur. since corticosteroids have anti-inflammatory and antifibrotic effects, we tested the ability of dexamethasone to ...201424695778
expression of chlamydia muridarum plasmid genes and immunogenicity of pgp3 and pgp4 in different mouse strains.chlamydia muridarum carries a cryptic plasmid (pmopn) of 7.5kb, which encodes seven genes. our aims were to describe the transcriptional pattern of the pmopn genes in c. muridarum-infected mice and to evaluate the host immune responses against pgp3 and pgp4 proteins. balb/c and c57bl/6n female mice were inoculated intranasally with c. muridarum and sacrificed at different time points, and the total rna was extracted from the lung suspensions to determine the levels of expression of the different ...201424631212
innate immunity is sufficient for the clearance of chlamydia trachomatis from the female mouse genital tract.chlamydia muridarum and chlamydia trachomatis, mouse and human strains, respectively, have been used to study immunity in a murine model of female genital tract infection. despite evidence that unique genes of these otherwise genomically similar strains could play a role in innate immune evasion in their respective mouse and human hosts, there have been no animal model findings to directly support this conclusion. here, we infected c57bl/6 and adaptive immune-deficient rag1(-/-) female mice with ...201424585717
signaling via tumor necrosis factor receptor 1 but not toll-like receptor 2 contributes significantly to hydrosalpinx development following chlamydia muridarum infection.chlamydial infection in the lower genital tract can lead to hydrosalpinx, which is accompanied by activation of both pattern recognition receptor tlr2- and inflammatory cytokine receptor tnfr1-mediated signaling pathways. in the current study, we compared the relative contributions of these two receptors to chlamydial induction of hydrosalpinx in mice. we found that mice with or without deficiencies in tlr2 or tnfr1 displayed similar time courses of live organism shedding from vaginal swabs, sug ...201424549331
evaluation of a multisubunit recombinant polymorphic membrane protein and major outer membrane protein t cell vaccine against chlamydia muridarum genital infection in three strains of mice.an efficacious vaccine is needed to control chlamydia trachomatis infection. in the murine model of chlamydia muridarum genital infection, multifunctional mucosal cd4 t cells are the foundation for protective immunity, with antibody playing a secondary role. we previously identified four chlamydia outer membrane proteins (pmpe, pmpf, pmpg and pmph) as cd4 t cell vaccine candidates using a dendritic cell-based immunoproteomic approach. we also demonstrated that these four polymorphic membrane pro ...201424992718
bioluminescence imaging of chlamydia muridarum ascending infection in mice.chlamydial pathogenicity in the upper genital tract relies on chlamydial ascending from the lower genital tract. to monitor chlamydial ascension, we engineered a luciferase-expressing c. muridarum. in cells infected with the luciferase-expressing c. muridarum, luciferase gene expression and enzymatic activity (measured as bioluminescence intensity) correlated well along the infection course, suggesting that bioluminescence can be used for monitoring chlamydial replication. following an intravagi ...201424983626
an atypical cd8 t-cell response to chlamydia muridarum genital tract infections includes t cells that produce interleukin-13.chlamydia trachomatis urogenital serovars d-k are intracellular bacterial pathogens that replicate almost exclusively in human reproductive tract epithelium. in the c. muridarum mouse model for human chlamydia genital tract infections cd4 t helper type 1 cell responses mediate protective immunity while cd8 t-cell responses have been associated with scarring and infertility. scarring mediated by cd8 t cells requires production of tumour necrosis factor-α (tnf-α); however, tnf-α is associated with ...201424428415
transformation of chlamydia muridarum reveals a role for pgp5 in suppression of plasmid-dependent gene expression.transformation of chlamydia trachomatis should greatly advance the chlamydial research. however, significant progress has been hindered by the failure of c. trachomatis to induce clinically relevant pathology in animal models. chlamydia muridarum, which naturally infects mice, can induce hydrosalpinx in mice, a tubal pathology also seen in women infected with c. trachomatis. we have developed a c. muridarum transformation system and confirmed pgp1, -2, -6, and -8 as plasmid maintenance factors, ...201424363344
reduced live organism recovery and lack of hydrosalpinx in mice infected with plasmid-free chlamydia muridarum.plasmid-free chlamydia trachomatis and chlamydia muridarum fail to induce severe pathology. to evaluate whether the attenuated pathogenicity is due to insufficient infection or inability of the plasmidless chlamydial organisms to trigger pathological responses, we compared plasmid-competent and plasmid-free c. muridarum infections in 5 different strains of mice. all 5 strains developed hydrosalpinx following intravaginal inoculation with plasmid-competent, but not inoculation with plasmid-free, ...201424343644
induction of the chlamydia muridarum stress/persistence response increases azithromycin treatment failure in a murine model of infection.viable but noninfectious (stressed/persistent) chlamydiae are more resistant to azithromycin (azm) in culture than are organisms in the normal developmental cycle. chlamydia muridarum-infected mice were exposed to amoxicillin to induce the organisms to enter the persistent/stressed state and subsequently treated with azm. azm treatment failure was observed in 22% of persistently infected mice, with an average of 321,667 inclusion-forming units (ifu) shed after azm treatment. productively infecte ...201424342653
induction of protective immunity against chlamydia muridarum intracervical infection in dba/1j mice.we previously reported that intracervical inoculation with chlamydia muridarum induced hydrosalpinx in dba/1j mice, but intravaginal inoculation failed to do so. in the current study, we found unexpectedly that intrabursal inoculation of live chlamydial organisms via the oviduct failed to induce significant hydrosalpinx. we further tested whether primary infection via intravaginal or intrabursal inoculation could induce protective immunity against hydrosalpinx following intracervical challenge i ...201424188757
early microrna expression profile as a prognostic biomarker for the development of pelvic inflammatory disease in a mouse model of chlamydial genital infection.it is not currently possible to predict the probability of whether a woman with a chlamydial genital infection will develop pelvic inflammatory disease (pid). to determine if specific biomarkers may be associated with distinct chlamydial pathotypes, we utilized two chlamydia muridarum variants (c. muridarum var001 [cmvar001] and cmvar004) that differ in their abilities to elicit upper genital tract pathology in a mouse model. cmvar004 has a lower growth rate in vitro and induces pathology in onl ...201424961692
[characteristic of early mucosal immune response in mice during intravaginal infection caused by chlamydia muridarum].comparison of features of recruitment to infection focus of cells mediating early immune reactions in intravaginally infected mice that had previously received or not received covinan (progesterone analogue).201422937700
guanylate binding proteins enable rapid activation of canonical and noncanonical inflammasomes in chlamydia-infected macrophages.interferon (ifn)-inducible guanylate binding proteins (gbps) mediate cell-autonomous host resistance to bacterial pathogens and promote inflammasome activation. the prevailing model postulates that these two gbp-controlled activities are directly linked through gbp-dependent vacuolar lysis. it was proposed that the rupture of pathogen-containing vacuoles (pvs) by gbps destroyed the microbial refuge and simultaneously contaminated the host cell cytosol with microbial activators of inflammasomes. ...201526416908
cd43-, but not cd43+, il-10-producing cd1dhicd5+ b cells suppress type 1 immune responses during chlamydia muridarum genital tract infection.regulatory b (breg) cells are known to modulate immune responses through predominantly interleukin-10 (il-10)-dependent mechanisms and can be hypothetically divided into innate and adaptive subsets based on the nature of their activating signals. however, the specific role of different breg subsets in modulating immune responses remains ambiguous. here we have shown that chlamydia induces il-10-producing splenic b-cell populations consisting of cd43(+) and cd43(-) subsets of igm(hi)igd(lo) innat ...201524938746
chlamydia muridarum infection associated host micrornas in the murine genital tract and contribution to generation of host immune response.chlamydia trachomatis (ct) is the leading sexually transmitted bacterial infection in humans and is associated with reproductive tract damage. however, little is known about the involvement and regulation of micrornas (mirs) in genital ct.201524976530
quantitative in vivo detection of chlamydia muridarum associated inflammation in a mouse model using optical imaging.chlamydia trachomatis is a bacterial sexually transmitted disease with over 1.3 million cases reported to the cdc in 2010. while chlamydia infection is easily treated with antibiotics, up to 70% of infections are asymptomatic and go untreated. the current mouse model relies on invasive upper genital tract gross pathology readouts at ~60-80 days postinfection. high throughput optical imaging through the use of biomarkers has been successfully used to quickly evaluate several disease processes. he ...201526663988
target cell limitation constrains chlamydial load in persistent infections: results from mathematical modelling applied to mouse genital tract infection data.the interactions between chlamydial pathogens and their host contribute to the outcome of infection. nonresolving infections in immunodeficient mice can provide insights into these mechanisms by allowing observation of a form of persistent infection. using a mathematical model, we predict that in a nonresolving infection, the number of chlamydiae in the host will attain a stable equilibrium and that this equilibrium will be independent of the inoculum size. we test this hypothesis by infecting r ...201525044245
the chromosome-encoded hypothetical protein tc0668 is an upper genital tract pathogenicity factor of chlamydia muridarum.we previously associated a missense mutation of the tc0668 gene of serial in vitro-passaged chlamydia muridarum, a murine model of human urogenital c. trachomatis, with severely attenuated disease development in the upper genital tract of female mice. since these mutants also contained a tc0237 q117e missense mutation that enhances their in vitro infectivity, an effort was made here to isolate and characterize a tc0668 single mutant to determine its individual contribution to urogenital pathogen ...201526597987
modeling the transcriptome of genital tract epithelial cells and macrophages in healthy mucosa versus mucosa inflamed by chlamydia muridarum infection.chlamydia trachomatis urogenital serovars are intracellular bacteria that parasitize human reproductive tract epithelium. as the principal cell type supporting bacterial replication, epithelial cells are central to chlamydia immunobiology initially as sentries and innate defenders, and subsequently as collaborators in adaptive immunity-mediated bacterial clearance. in asymptomatic individuals who do not seek medical care a decisive struggle between c. trachomatis and host defenses occurs at the ...201526519447
a vaccine formulated with the major outer membrane protein can protect c3h/hen, a highly susceptible strain of mice, from a chlamydia muridarum genital challenge.c3h/hen female mice were vaccinated with native chlamydia muridarum major outer membrane protein (momp), using montanide+cpg or alum+cpg as adjuvants. negative control groups were immunized with ovalbumin (ova) and the same adjuvants. as positive control, mice were inoculated intranasally with live chlamydia. mice were challenged in the ovarian bursa with 10(5) c. muridarum inclusion forming units. six weeks after the genital challenge the animals were caged with male mice and monitored for preg ...201526423798
pulmonary chlamydia muridarum challenge activates lung interstitial macrophages which correlate with ifn-γ production and infection control in mice.protective immunity to the pathogen chlamydia is dependent on a robust ifn-γ response generated by innate and adaptive lymphocytes. here we assess the role of the macrophage in orchestrating a protective response in vivo to the murine pathogen, chlamydia muridarum. during acute pulmonary and peritoneal infection, resident macrophages in both sites are infected with c. muridarum and adopt an inflammatory phenotype. in the lung, this activation is restricted to interstitial macrophages, which harb ...201526344246
role of stat1 in chlamydia-induced type-1 interferon production in oviduct epithelial cells.we previously reported that chlamydia muridarum-infected murine oviduct epithelial cells (oe cells) secrete interferon β (ifn-β) in a mostly tlr3-dependent manner. however, c. muridarum-infected tlr3-deficient oe cells were still able to secrete detectable levels of ifn-β into the supernatants, suggesting that other signaling pathways contribute to chlamydia-induced ifn-β synthesis in these cells. we investigated the role of stat1 as a possible contributor in the chlamydia-induced type-1 ifn pro ...201526262558
nk cells modulate the lung dendritic cell-mediated th1/th17 immunity during intracellular bacterial infection.the impact of the interaction between nk cells and lung dendritic cells (ldcs) on the outcome of respiratory infections is poorly understood. in this study, we investigated the effect and mechanism of nk cells on the function of ldcs during intracellular bacterial lung infection of chlamydia muridarum in mice. we found that the naive mice receiving ldcs from c. muridarum-infected nk-cell-depleted mice (nk-ldcs) showed more serious body weight loss, bacterial burden, and pathology upon chlamydial ...201526222048
[role of light signal pathway in chlamydia muridarum urogenital infection in mice].to study the role of lymphotoxin-like inducible protein that competes with glycoprotein d for herpesvirus entry on t cells (light) in the development of protective immunity and pathology during chlamydia muridarum urogenital infection in mice.201526211324
in vivo and ex vivo imaging reveals a long-lasting chlamydial infection in the mouse gastrointestinal tract following genital tract inoculation.intravaginal infection with chlamydia muridarum in mice can ascend to the upper genital tract, resulting in hydrosalpinx, a pathological hallmark for tubal infertility in women infected with c. trachomatis. here, we utilized in vivo imaging of c. muridarum infection in mice following an intravaginal inoculation and confirmed the rapid ascent of the chlamydial organisms from the lower to upper genital tracts. unexpectedly, the c. muridarum-derived signal was still detectable in the abdominal area ...201526099591
identification of plasmid-free chlamydia muridarum organisms using a pgp3 detection-based immunofluorescence assay.chlamydia possesses a conserved 7.5 kb plasmid that is known to play an important role in chlamydial pathogenesis, since some chlamydial organisms lacking the plasmid are attenuated. the chlamydial transformation system developed recently required the use of plasmid-free organisms. thus, the generation and identification of plasmid-free organisms represent a key step in understanding chlamydial pathogenic mechanisms. a tricolor immunofluorescence assay for simultaneously detecting the plasmid-en ...201526059520
chlamydia muridarum infection of macrophages elicits bactericidal nitric oxide production via reactive oxygen species and cathepsin b.the ability of certain species of chlamydia to inhibit the biogenesis of phagolysosomes permits their survival and replication within macrophages. the survival of macrophage-adapted chlamydiae correlates with the multiplicity of infection (moi), and optimal chlamydial growth occurs in macrophages infected at an moi of ≤1. in this study, we examined the replicative capacity of chlamydia muridarum in the raw 264.7 murine macrophage cell line at different mois. c. muridarum productively infected th ...201526015483
plasmid-encoded pgp5 is a significant contributor to chlamydia muridarum induction of hydrosalpinx.we have previously shown that the plasmid-encoded pgp3 is a major virulence factor for c. muridarum induction of hydrosalpinx. we now report that pgp5 also plays a significant role in the development of hydrosalpinx following c. muridarum induction. pgp5 deficiency was introduced via either in-frame deletion (cm-δpgp5) or premature stop codon installation (cm-pgp5s). mice infected with either cm-δpgp5 or cm-pgp5s developed hydrosalpinges at significantly reduced levels with an incidence rate of ...201525915629
[th17 lymphocytes in bacterial infections].th17 cells are a relatively newly discovered subpopulation of helper cd4+ t lymphocytes. it has been shown that these cells may contribute to tissue damage during certain inflammatory and autoimmune diseases and also play an important role in antitumor and antimicrobial, particularly antibacterial, immunity. bacteria stimulate the th17 response through several toll-like (tlr), nod-like (nlr) and c-type lectin (clr) receptors. when activated, th17 lymphocytes produce several cytokines, mainly int ...201525897100
intrauterine infection with plasmid-free chlamydia muridarum reveals a critical role of the plasmid in chlamydial ascension and establishes a model for evaluating plasmid-independent pathogenicity.intravaginal infection with plasmid-competent but not plasmid-free chlamydia muridarum induces hydrosalpinx in mouse upper genital tract, indicating a critical role of the plasmid in chlamydial pathogenicity. to evaluate the contribution of the plasmid to chlamydial ascension and activation of tubal inflammation, we delivered plasmid-free c. muridarum directly into the endometrium by intrauterine inoculation. we found that three of the six mouse strains tested, including cba/j, c3h/hej, and c57b ...201525870225
murine microrna-214 regulates intracellular adhesion molecule (icam1) gene expression in genital chlamydia muridarum infection.the hallmark of chlamydial infection is the development of upper genital pathology in the form of hydrosalpinx and oviduct and/or tubal dilatation. although molecular events leading to genital tissue presentation and cellular architectural remodelling are unclear, early-stage host immune responses are believed to contribute to these long-term sequelae. recently, we reported the contribution of selected infection-associated micrornas (mirs) in the generation of host immunity at early-stage infect ...201525865776
chlamydia muridarum induction of glandular duct dilation in mice.although chlamydia-induced hydrosalpinx in women and mice has been used as a surrogate marker for tubal infertility, the medical relevance of nontubal pathologies, such as uterine horn dilation, developed in mice following chlamydial infection remains unclear. we now report that the uterine horn dilation correlates with glandular duct dilation detected microscopically following chlamydia muridarum infection. the dilated glandular ducts pushed the uterine horn lumen to closure or dilation and eve ...201525824829
outer membrane proteins preferentially load mhc class ii peptides: implications for a chlamydia trachomatis t cell vaccine.cd4 t cell immune responses such as interferon-γ and tumor necrosis factor-α secretion are necessary for chlamydia immunity. we used an immunoproteomic approach in which chlamydia trachomatis and chlamydia muridarum-derived peptides presented by mhc class ii molecules on the surface of infected dendritic cells (dcs) were identified by tandem mass spectrometry using bone marrow derived dcs (bmdcs) from mice of different mhc background. we first compared the c. muridarum immunoproteome in c3h mice ...201525738816
in vitro passage selects for chlamydia muridarum with enhanced infectivity in cultured cells but attenuated pathogenicity in mouse upper genital tract.although modern chlamydia muridarum has been passaged for decades, there are no reports on the consequences of serial passage with strong selection pressure on its fitness. in order to explore the potential for pasteurian selection to induce genomic and phenotypic perturbations to c. muridarum, a starter population was passaged in cultured cells for 28 generations without standard infection assistance. the resultant population, designated cmg28, displays markedly reduced in vitro dependence on c ...201525712926
genomic variant representation in a chlamydia population is dynamic and adaptive with dependence on in vitro and in vivo passage.we have previously shown that chlamydia muridarum has multiple genomic variants that concomitantly vary in their in vitro and in vivo phenotype. herein, we used real-time polymerase chain reaction-based genotyping assays to query plaque-cloned isolates of c. muridarum for the frequency of eight selected polymorphisms. these strains had no history of passage in vivo since their original isolation from laboratory mice. there was significant variance in the frequency of two of the eight polymorphis ...201525673672
chlamydial lung infection induces transient il-9 production which is redundant for host defense against primary infection.il-9/th9 responses are recently found to be important for innate and adaptive immunity particularly in parasitic infections. to date, the study on the role of il-9 in bacterial infections is limited and the reported data are contradictory. one reported function of il-9/th9 is to modulate th1/th17 responses. since our and others' previous work has shown a critical role of th1 and th17 cells in host defense against chlamydial lung infection, we here examined the role of il-9 responses in chlamydia ...201525646821
high chlamydia burden promotes tumor necrosis factor-dependent reactive arthritis in skg mice.chlamydia trachomatis is a sexually transmitted obligate intracellular pathogen that causes inflammatory reactive arthritis, spondylitis, psoriasiform dermatitis, and conjunctivitis in some individuals after genital infection. the immunologic basis for this inflammatory response in susceptible hosts is poorly understood. as zap-70(w163c) -mutant balb/c (skg) mice are susceptible to spondylo-arthritis after systemic exposure to microbial β-glucan, we undertook the present study to compare respons ...201525624153
tumor necrosis factor (tnf) receptor superfamily member 1b on cd8+ t cells and tnf receptor superfamily member 1a on non-cd8+ t cells contribute significantly to upper genital tract pathology following chlamydial infection.we demonstrated previously that tumor necrosis factor α (tnf-α)-producing chlamydia-specific cd8(+) t cells cause oviduct pathological sequelae.201525552370
chlamydia muridarum infection-induced destruction of male germ cells and sertoli cells is partially prevented by chlamydia major outer membrane protein-specific immune cd4 cells.chlamydia trachomatis infections are increasingly prevalent worldwide. male chlamydial infections are associated with urethritis, epididymitis, and orchitis; however, the role of chlamydia in prostatitis and male factor infertility remains controversial. using a model of chlamydia muridarum infection in male c57bl/6 mice, we investigated the effects of chlamydial infection on spermatogenesis and determined the potential of immune t cells to prevent infection-induced outcomes. antigen-specific cd ...201525472923
mutational analysis of the chlamydia muridarum plasticity zone.pathogenically diverse chlamydia spp. can have surprisingly similar genomes. chlamydia trachomatis isolates that cause trachoma, sexually transmitted genital tract infections (chlamydia), and invasive lymphogranuloma venereum (lgv) and the murine strain chlamydia muridarum share 99% of their gene content. a region of high genomic diversity between chlamydia spp. termed the plasticity zone (pz) may encode niche-specific virulence determinants that dictate pathogenic diversity. we hypothesized tha ...201525939505
analyses of the pathways involved in early- and late-phase induction of ifn-beta during c. muridarum infection of oviduct epithelial cells.we previously reported that the ifn-β secreted by chlamydia muridarum-infected murine oviduct epithelial cells (oe cells) was mostly dependent on the tlr3 signaling pathway. to further characterize the mechanisms of ifn-β synthesis during chlamydia infection of oe cells in vitro, we utilized specific inhibitory drugs to clarify the roles of irf3 and nf-κb on both early- and late-phase c. muridarum infections. our results showed that the pathways involved in the early-phase of ifn-β production we ...201525798928
ifn-ε protects primary macrophages against hiv infection.ifn-ε is a unique type i ifn that is not induced by pattern recognition response elements. ifn-ε is constitutively expressed in mucosal tissues, including the female genital mucosa. although the direct antiviral activity of ifn-ε was thought to be weak compared with ifn-α, ifn-ε controls chlamydia muridarum and herpes simplex virus 2 in mice, possibly through modulation of immune response. we show here that ifn-ε induces an antiviral state in human macrophages that blocks hiv-1 replication. ifn- ...201627942584
tetracycline selective pressure and homologous recombination shape the evolution of chlamydia suis: a recently identified zoonotic pathogen.species closely related to the human pathogen chlamydia trachomatis (ct) have recently been found to cause zoonotic infections, posing a public health threat especially in the case of tetracycline resistant chlamydia suis (cs) strains. these strains acquired a tet(c)-containing cassette via horizontal gene transfer (hgt). genomes of 11 cs strains from various tissues were sequenced to reconstruct evolutionary pathway(s) for tet(c) hgt. cs had the highest recombination rate of chlamydia species s ...201627576537
chlamydial pre-infection protects from subsequent herpes simplex virus-2 challenge in a murine vaginal super-infection model.chlamydia trachomatis and herpes simplex virus-2 (hsv-2) genital tract co-infections have been reported in humans and studied in vitro but the clinical consequences are unknown. limited epidemiologic evidence suggests that these co-infections could be more severe than single infections of either pathogen, but the host-pathogen interactions during co-infection remain uncharacterized. to determine whether disease progression and/or pathogen shedding differs between singly-infected and super-infect ...201626726882
ifnγ is required for optimal antibody-mediated immunity against genital chlamydia infection.defining the mechanisms of immunity conferred by the combination of antibody and cd4(+) t cells is fundamental to designing an efficacious chlamydial vaccine. using the chlamydia muridarum genital infection model of mice, which replicates many features of human c. trachomatis infection and avoids the characteristic low virulence of c. trachomatis in the mouse, we previously demonstrated a significant role for antibody in immunity to chlamydial infection. we found that antibody alone was not prot ...201627600502
chlamydia trachomatis is resistant to inclusion ubiquitination and associated host defense in gamma interferon-primed human epithelial cells.the cytokine gamma interferon (ifn-γ) induces cell-autonomous immunity to combat infections with intracellular pathogens, such as the bacterium chlamydia trachomatis the present study demonstrates that ifn-γ-primed human cells ubiquitinate and eliminate intracellular chlamydia-containing vacuoles, so-called inclusions. we previously described how ifn-γ-inducible immunity-related gtpases (irgs) employ ubiquitin systems to mark inclusions for destruction in mouse cells and, furthermore, showed tha ...201627965446
antigen specific immune response in chlamydia muridarum genital infection is dependent on murine micrornas-155 and -182.anti-chlamydial immunity involves efficient presentation of antigens (ag) to effector cells resulting in ag-specific immune responses. there is limited information on inherent underlying mechanisms regulating these events. previous studies from our laboratory have established that select micrornas (mirs) function as molecular regulators of immunity in chlamydia muridarum (cm) genital infection. in this report, we investigated immune cell type-specific mirs, i.e. mir-155 and -182, and the role in ...201627556515
host nectin-1 promotes chlamydial infection in the female mouse genital tract, but is not required for infection in a novel male murine rectal infection model.chlamydia trachomatis is the most common bacterial sexually transmitted pathogen, but more than 70% of patients fail to seek treatment due to the asymptomatic nature of these infections. women suffer from numerous complications from chronic chlamydial infections, which include pelvic inflammatory disease and infertility. we previously demonstrated in culture that host cell nectin-1 knockdown significantly reduced chlamydial titers and inclusion size. here, we sought to determine whether nectin-1 ...201627486990
mri as a novel in vivo approach for assessing structural changes of chlamydia pathology in a mouse model.chlamydia trachomatis is among the most prevalent of sexually transmitted diseases. while chlamydia infection is a reportable event and screening has increased over time, enhanced surveillance has not resulted in a reduction in the rate of infections, and chlamydia infections frequently recur. the development of a preventative vaccine for chlamydia may be the only effective approach for reducing infection and the frequency of pathological outcomes. current vaccine research efforts involve time c ...201627467585
ccl19-ccr7-dependent reverse transendothelial migration of myeloid cells clears chlamydia muridarum from the arterial intima.regions of the normal arterial intima predisposed to atherosclerosis are sites of ongoing monocyte trafficking and also contain resident myeloid cells with features of dendritic cells. however, the pathophysiological roles of these cells are poorly understood. here we found that intimal myeloid cells underwent reverse transendothelial migration (rtm) into the arterial circulation after systemic stimulation of pattern-recognition receptors (prrs). this process was dependent on expression of the c ...201627668800
intravenous inoculation with chlamydia muridarum leads to a long-lasting infection restricted to the gastrointestinal tract.chlamydia has been detected in the gastrointestinal tracts of both animals and humans. however, it remains unclear whether the chlamydial organisms can be introduced into the gastrointestinal tract via pathways independent of the oral and anal routes. we have recently shown that chlamydia muridarum spreads from the genital tract to the gastrointestinal tract potentially via the circulatory system. to test whether hematogenous c. muridarum can spread to and establish a long-lasting colonization i ...201627271744
the chlamydia muridarum organisms fail to auto-inoculate the mouse genital tract after colonization in the gastrointestinal tract for 70 days.chlamydia muridarum is known to colonize in the gastrointestinal tract for long periods of time, which has been hypothesized to serve as a reservoir for spreading to the genital tract. to test this hypothesis, a luciferase-expressing c. muridarum was used to establish a long-lasting infection in the mouse gastrointestinal tract following either intragastric or intrarectal inoculations. in vivo imaging revealed significant bioluminescent signals mainly in the mouse abdominal area throughout the e ...201627192556
biophysical principles predict fitness landscapes of drug resistance.fitness landscapes of drug resistance constitute powerful tools to elucidate mutational pathways of antibiotic escape. here, we developed a predictive biophysics-based fitness landscape of trimethoprim (tmp) resistance for escherichia coli dihydrofolate reductase (dhfr). we investigated the activity, binding, folding stability, and intracellular abundance for a complete set of combinatorial dhfr mutants made out of three key resistance mutations and extended this analysis to dhfr originated from ...201626929328
involvement of lysosome membrane permeabilization and reactive oxygen species production in the necrosis induced by chlamydia muridarum infection in l929 cells.chlamydiae, obligate intracellular bacteria, are associated with a variety of human diseases. the chlamydial life cycle undergoes a biphasic development: replicative reticulate bodies (rbs) phase and infectious elementary bodies (ebs) phase. at the end of the chlamydial intracellular life cycle, ebs have to be released to the surrounded cells. therefore, the interactions between chlamydiae and cell death pathways could greatly influence the outcomes of chlamydia infection. however, the underlyin ...201626838343
iga modulates respiratory dysfunction as a sequela to pulmonary chlamydial infection as neonates.neonatal chlamydia lung infections are associated with serious sequelae such as asthma and airway hyper-reactivity in children and adults. our previous studies demonstrated the importance of th-1 type cytokines, il-12 and ifn-γ in protection against neonatal pulmonary chlamydial challenge; however, the role of the humoral arm of defense has not been elucidated. we hypothesized that b-cells and iga, the major mucosal antibody, play a protective role in newborns against development of later life r ...201626755533
detection of chlamydia infection in peromyscus species rodents from sylvatic and laboratory sources.to determine if chlamydia muridarum, or other chlamydiae, are enzootic in rodents, we probed a serum bank of wild peromyscus spp. mice for immunoglobulin g-antibody reactivity to ultraviolet light-inactivated c. muridarum elementary bodies (ebs) using an enzyme-linked immunoassay. applying a cut-off for a positive reaction of od(405) nm = 0.1 at a 1:20 dilution, we found titratable antibody reactivity in 190 of 247 specimens surveyed (77%, mean od(405) = 0.33 ± 0.26, range = 0.11-1.81, median = ...201626733499
computational modeling of tc0583 as a putative component of the chlamydia muridarum v-type atp synthase complex and assessment of its protective capabilities as a vaccine antigen.numerous chlamydia trachomatis proteins have been identified as potential subunit vaccines, of which the major outer-membrane protein (momp) has, so far, proven the most efficacious. recently, subunit a of the v-type atp synthase (atpase; tc0582) complex was shown to elicit partial protection against infection. computational modeling of a neighboring gene revealed a novel subunit of the v-type atpase (tc0583). to determine if this newly identified subunit could induce protection and/or enhance t ...201626706820
the p47phox deficiency significantly attenuates the pathogenicity of chlamydia muridarum in the mouse oviduct but not uterine tissues.the chlamydia muridarum induction of the upper genital tract pathology in mice has been used to investigate the mechanisms of chlamydial pathogenesis. we report that the ncf1 (neutrophil cytosolic factor1)-encoded p47phox (phagocyte oxidase), an essential subunit of nicotinamide adenine dinucleotide phosphate (nadph)-oxidase, contributes significantly to c. muridarum induction of hydrosalpinx. mice lacking p47phox (p47phox-deficient) were no longer able to develop significant hydrosalpinx follow ...201626645958
il-17e production is elevated in the lungs of balb/c mice in the later stages of chlamydia muridarum infection and re-infection.pathogens can influence allergic respiratory diseases. we previously found that multiple infections with chlamydophila pneumoniae induce the production of interleukin-17a (il-17a) and il-17e, which have roles in the pathogenesis of asthma. the present work was designed to investigate our hypothesis that infections with another pathogen can induce the production of il-17a and il-17e.201624292583
mechanism of t-cell mediated protection in newborn mice against a chlamydia infection.to determine the immune components needed for protection of newborn mice against chlamydia muridarum, animals born to chlamydia-immunized and to sham-immunized dams were infected intranasally with c. muridarum at 2 post-natal days. t-cells isolated from immunized or sham-immunized adult mice were adoptively transferred to newborn mice at the time of infection. also, to establish what cytokines are involved in protection, ifn-γ, tnf-α, il-10, and il-12 were passively transferred to newborn mice. ...201723644176
a chlamydia-specific tcr-transgenic mouse demonstrates th1 polyfunctionality with enhanced effector function.chlamydia is responsible for millions of new infections annually, and current efforts focus on understanding cellular immunity for targeted vaccine development. the chlamydia-specific cd4 t cell response is characterized by the production of ifn-γ, and polyfunctional th1 responses are associated with enhanced protection. a major limitation in studying these responses is the paucity of tools available for detection, quantification, and characterization of polyfunctional ag-specific t cells. we ad ...201728855311
ccr7 deficiency allows accelerated clearance of chlamydia from the female reproductive tract.immune mechanisms responsible for pathogen clearance from the female reproductive tract (frt) are incompletely defined; in particular, the contribution of lymphocyte trafficking to this process is unclear. ccr7-deficient mice have profoundly altered lymphocyte recirculation and display ectopic formation of lymphocyte aggregates within mucosal nonlymphoid tissues, including the frt. in this study, we investigated how altered lymphocyte distribution in ccr7-deficient mice would affect host respons ...201728801359
Refresh
firstprev
1234
nextlast
Displaying items 201 - 300 of 323